{"gene":"COBL","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2011,"finding":"Cobl forms complexes with syndapin I in vivo (coimmunoprecipitation, colocalization, subcellular recruitment). Syndapin I recruits Cobl to membranes via its F-BAR domain (in vitro reconstitution and subcellular fractionation). Syndapin I RNAi impairs cortical localization of Cobl. Cobl, syndapin I, and N-WASP co-exist in one complex. Cobl-mediated functions in neuronal morphogenesis (dendritic arbor development) critically rely on syndapin I and on Arp3.","method":"Coimmunoprecipitation, colocalization, subcellular fractionation, in vitro reconstitution, RNAi knockdown with neuronal morphology readout","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (Co-IP, in vitro reconstitution, fractionation, functional RNAi rescue) in a single focused study","pmids":["21725280"],"is_preprint":false},{"year":2012,"finding":"Cobl plays a crucial role in Purkinje cell dendritic arborization (branch point number, density, and higher-order branching). Cobl physically associates with the F-actin-binding protein Abp1 (subcellular fractionation, protein interaction analysis, reconstitution, colocalization). Cobl-mediated dendritic branch induction critically relies on Abp1, and a Cobl mutant deficient for Abp1 binding fails to rescue Cobl loss-of-function phenotypes. Abp1-mediated F-actin association is required for Cobl function, as an Abp1 mutant supporting Cobl association but lacking F-actin binding also failed to rescue.","method":"Gene gun transfection in cerebellar slices, RNAi knockdown, subcellular fractionation, protein interaction/co-IP, subcellular reconstitution, colocalization, functional rescue with point mutants","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods including mutagenesis-based rescue experiments establishing functional requirement of the Cobl-Abp1 interaction","pmids":["23223303"],"is_preprint":false},{"year":2012,"finding":"In zebrafish, Cobl and syndapin I colocalize at the base of forming cilia and are both required for formation of kinocilia and F-actin-rich stereocilia in lateral line sensory hair cells. Proper formation of ciliated sensory hair cell rosettes requires Cobl's syndapin I-binding Cobl homology domain and the actin-nucleating C-terminus of Cobl. Loss of Cobl or syndapin I causes similar lateral line defects, supporting they function together.","method":"Morpholino knockdown in zebrafish, scanning electron microscopy, colocalization, rescue experiments with domain mutants","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — parallel loss-of-function studies in zebrafish with domain-specific rescue experiments and EM phenotyping","pmids":["23203810"],"is_preprint":false},{"year":2015,"finding":"Cobl actin nucleation activity requires all three of its WH2 domains. Cobl is directly regulated by Ca2+/calmodulin (CaM): Ca2+/CaM modulates Cobl's actin-binding properties and promotes Cobl's interactions with syndapin I. CaM inhibitor studies showed Cobl-mediated dendritic branching is strictly dependent on CaM activity. Cobl-induced dendritic branch initiation was preceded by Ca2+ signals and coincided with local F-actin and CaM accumulations. CaM-binding-defective Cobl mutants failed to rescue Cobl loss-of-function phenotypes.","method":"Overexpression and rescue experiments in primary neurons and tissue slices, CaM inhibitor studies, Ca2+ imaging, in vitro actin binding/nucleation assays, mutagenesis of CaM-binding sites","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro biochemical reconstitution combined with mutagenesis-based neuronal rescue and live Ca2+ imaging in a single focused study","pmids":["26334624"],"is_preprint":false},{"year":2018,"finding":"Cobl is controlled by arginine methylation via PRMT2. PRMT2 associates with Cobl in an SH3 domain-dependent manner (coprecipitation, Co-IP, cellular and in vitro reconstitutions), and this promotes methylation of Cobl's actin-nucleating C-terminal domain. Cobl methylation is key for Cobl actin binding. PRMT2 phenocopies Cobl in gain- and loss-of-function dendritogenesis assays. Cobl-mediated dendritic arborization required complex formation with PRMT2 and PRMT2's catalytic activity.","method":"Coprecipitation, coimmunoprecipitation, cellular and in vitro reconstitution, gain- and loss-of-function in neurons, catalytic mutant of PRMT2, actin binding assays","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution of methylation, mutagenesis of catalytic domain, and multiple cellular assays establishing mechanistic requirement","pmids":["29689199"],"is_preprint":false},{"year":2018,"finding":"Cobl is required for postnatal planar cell polarity refinement in cochlear hair cells. Cobl KO mice show reduced F-actin beneath the sensory apparatus, premature kinocilium retraction, and mispositioned basal bodies/centrioles during the critical period of hearing onset. Pericentriolar scaffold defects in Cobl KO mice are actin polymerization-dependent and Ca2+/calmodulin signaling-dependent.","method":"Cobl KO mouse analysis, F-actin staining, centriole/basal body positioning imaging, Ca2+/CaM inhibitor treatment, actin polymerization inhibitor treatment","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO mouse with mechanistic dissection using pharmacological inhibitors linking Cobl to actin polymerization and Ca2+/CaM pathways","pmids":["30157434"],"is_preprint":false},{"year":2020,"finding":"COBL physically interacts with and is stabilized by IGFN1 in skeletal muscle. COBL localizes to the Z-disc in adult muscle. IGFN1 interaction prevents COBL's ability to form actin ruffles in COS7 cells. COBL is expressed in differentiating C2C12 myoblasts but not in proliferating cells. COBL loss-of-function C2C12 clones are able to fuse, indicating COBL is not essential for myoblast fusion.","method":"Pulldown with IGFN1 fragments followed by proteomics, co-IP validation, colocalization imaging, COS7 cell actin ruffle assay, COBL KO C2C12 clones","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — proteomic pulldown with validation by co-IP and functional assay in COS7 cells, single lab","pmids":["32768501"],"is_preprint":false},{"year":2021,"finding":"Cobl and Cobl-like act interdependently in dendritic arbor development; neither alone is sufficient. Syndapin I physically links Cobl and Cobl-like by forming nanodomains at convex plasma membrane areas at protrusion bases and interacting with three motifs in Cobl-like, one of which is Ca2+/calmodulin-regulated. Cobl-like's N-terminal calmodulin-binding site and Ca2+/CaM-responsive syndapin-binding motif are both critical for Cobl-like's dendritogenic function.","method":"Co-IP, colocalization, TIRF/superresolution imaging of syndapin nanodomains, loss-of-function and rescue experiments with domain/point mutants in neurons","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, superresolution imaging, domain-specific mutagenesis-based rescue) establishing interdependence and physical linkage mechanism","pmids":["34264190"],"is_preprint":false},{"year":2021,"finding":"Cobl is required for poststroke dendritic arbor repair in peri-infarct penumbral neurons. Ischemic stroke and excitotoxicity cause calpain-mediated proteolysis of Cobl, significantly reducing Cobl levels. Cobl levels are subsequently restored by increased mRNA expression. In Cobl KO mice, the dendritic repair window (day 2-4 post-stroke) passed without dendritic regrowth, demonstrating Cobl is causally required for poststroke recovery.","method":"Mouse MCAO model, Cobl KO mice, dendritic morphometry, calpain inhibitor treatment, mRNA quantification","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO mouse with causal rescue window analysis and identified proteolytic mechanism (calpain), replicated across multiple time points","pmids":["34898601"],"is_preprint":false},{"year":2025,"finding":"Cobl is expressed in ameloblasts during amelogenesis, particularly during the secretory phase, and colocalizes with actin filaments at the cell cortex. Cobl KO causes increased ameloblast height, increased apical F-actin at P0, and reduced apical F-actin density during maturation phase. Cobl-deficient mice show altered enamel composition (increased carbon content) and increased enamel surface area, demonstrating Cobl's role in actin cytoskeletal organization during enamel formation.","method":"Cobl KO mouse analysis, immunofluorescence colocalization, F-actin density quantification, enamel composition analysis","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with cellular and compositional phenotypes but single lab, no biochemical reconstitution","pmids":["40072087"],"is_preprint":false},{"year":2025,"finding":"Cobl KO mice lack a transient cortical dendritic arbor expansion that occurs during emerging adulthood (in layer V during adolescence and layer II/III during emerging adulthood in somatosensory, prefrontal, and motor cortex). This expansion is accompanied by transient dendritic spine length changes, linking the process to actin dynamics. Cobl is thus the first molecular component identified as required for emerging adulthood-related neuronal arbor changes during brain maturation.","method":"Cobl KO mouse, dendritic morphometry at multiple developmental time points across cortical layers","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with time- and layer-resolved phenotyping, but single lab and no direct biochemical mechanism in this study","pmids":["40555515"],"is_preprint":false}],"current_model":"COBL (Cordon-Bleu) is a WH2 domain-based actin nucleator that requires all three of its WH2 domains for activity; it is recruited to membranes by syndapin I (via its F-BAR domain), regulated by direct Ca²⁺/calmodulin binding (which modulates actin binding and promotes syndapin I interaction), and further controlled by PRMT2-mediated arginine methylation of its C-terminal nucleating domain; in neurons, Cobl works in concert with Abp1 (F-actin anchoring) and interdependently with Cobl-like (physically coordinated by syndapin I) to drive dendritic branch initiation and arborization, and is also required for sensory hair cell ciliogenesis, cochlear planar cell polarity refinement, poststroke dendritic repair, ameloblast cytoskeletal organization, and cortical dendritic arbor expansion during emerging adulthood."},"narrative":{"mechanistic_narrative":"COBL (Cordon-Bleu) is a WH2 domain-based actin nucleator that drives membrane-coupled actin cytoskeletal remodeling underlying neuronal dendritic branching and ciliary/cortical morphogenesis [PMID:21725280, PMID:26334624]. Its nucleating activity requires all three of its C-terminal WH2 domains and is gated by multiple inputs: direct Ca²⁺/calmodulin binding modulates its actin-binding properties and promotes its association with syndapin I, while PRMT2-mediated arginine methylation of the actin-nucleating C-terminal domain is required for efficient actin binding [PMID:26334624, PMID:29689199]. COBL is recruited to membranes by the F-BAR protein syndapin I and acts together with the F-actin-anchoring protein Abp1, with mutants defective for either partner failing to rescue loss-of-function phenotypes, establishing both interactions as functionally essential [PMID:21725280, PMID:23223303]. In dendritic arbor development COBL operates interdependently with its paralog Cobl-like, the two being physically linked by syndapin I nanodomains at convex protrusion-base membranes [PMID:34264190]. Beyond dendritogenesis, COBL is required for sensory hair cell ciliogenesis and cochlear planar cell polarity refinement [PMID:23203810, PMID:30157434], poststroke dendritic repair where it is cleaved by calpain and re-expressed during a defined repair window [PMID:34898601], ameloblast cortical actin organization during enamel formation [PMID:40072087], and a transient cortical dendritic arbor expansion during emerging adulthood [PMID:40555515]. In skeletal muscle COBL localizes to the Z-disc and is stabilized by IGFN1, which suppresses its actin-ruffling activity [PMID:32768501].","teleology":[{"year":2011,"claim":"Established how COBL, a cytosolic actin nucleator, is targeted to the membrane sites where it acts, answering how nucleation is spatially controlled during dendritic morphogenesis.","evidence":"Co-IP, colocalization, subcellular fractionation, in vitro reconstitution and RNAi with neuronal morphology readout","pmids":["21725280"],"confidence":"High","gaps":["Did not resolve how syndapin I binding is itself regulated","Structural basis of the Cobl–syndapin I–N-WASP complex not defined"]},{"year":2012,"claim":"Identified Abp1 as an essential F-actin-anchoring partner, showing COBL-nucleated actin must be physically coupled to existing filaments to induce dendritic branches.","evidence":"Gene gun transfection in cerebellar slices, RNAi, fractionation, reconstitution and point-mutant rescue","pmids":["23223303"],"confidence":"High","gaps":["Stoichiometry and order of Cobl–Abp1–F-actin assembly unresolved","Whether Abp1 coupling is required in non-Purkinje cell contexts not tested"]},{"year":2012,"claim":"Extended COBL function beyond dendrites to ciliogenesis, showing the same syndapin I-binding and actin-nucleating domains build F-actin-rich stereocilia and kinocilia in sensory hair cells.","evidence":"Morpholino knockdown in zebrafish, scanning EM, colocalization and domain-mutant rescue","pmids":["23203810"],"confidence":"High","gaps":["Mechanism linking cortical actin nucleation to ciliary base assembly not defined","Whether mammalian hair cells use the identical domain requirements not tested here"]},{"year":2015,"claim":"Defined the catalytic requirement (all three WH2 domains) and a direct Ca²⁺/calmodulin regulatory input, explaining how local Ca²⁺ signals trigger COBL-driven branch initiation.","evidence":"In vitro actin nucleation/binding assays, CaM inhibitor and Ca²⁺ imaging, CaM-binding mutant rescue in neurons","pmids":["26334624"],"confidence":"High","gaps":["Upstream source of the triggering Ca²⁺ signal not identified","Quantitative relationship between CaM occupancy and nucleation rate not measured"]},{"year":2018,"claim":"Revealed a post-translational control layer in which PRMT2-catalyzed arginine methylation of the nucleating domain is required for COBL actin binding and dendritogenesis.","evidence":"Co-IP, in vitro and cellular methylation reconstitution, PRMT2 catalytic mutant and gain/loss-of-function in neurons","pmids":["29689199"],"confidence":"High","gaps":["Specific methylated arginine residues and their individual contributions not mapped","Interplay between methylation and Ca²⁺/CaM regulation not resolved"]},{"year":2018,"claim":"Demonstrated an in vivo requirement for COBL in cochlear planar cell polarity refinement, tying its actin and Ca²⁺/CaM functions to centriole/basal body positioning during the critical period of hearing onset.","evidence":"Cobl KO mouse, F-actin and centriole imaging, actin-polymerization and Ca²⁺/CaM inhibitor treatment","pmids":["30157434"],"confidence":"High","gaps":["Molecular link between cortical actin and basal body anchoring not defined","Whether the same partner set (syndapin I, Abp1) operates here not tested"]},{"year":2020,"claim":"Identified IGFN1 as a muscle-specific stabilizing partner that localizes COBL to the Z-disc and suppresses its actin-ruffling activity, indicating context-dependent restraint of COBL function.","evidence":"IGFN1 fragment pulldown with proteomics, co-IP, colocalization, COS7 ruffle assay and COBL KO C2C12 clones","pmids":["32768501"],"confidence":"Medium","gaps":["Single lab; physiological consequence of COBL–IGFN1 at the Z-disc not established in vivo","Mechanism by which IGFN1 blocks ruffling not defined"]},{"year":2021,"claim":"Resolved how COBL and its paralog Cobl-like coordinate during dendritogenesis, showing syndapin I nanodomains physically link the two factors at convex membrane bases and that neither is sufficient alone.","evidence":"Co-IP, TIRF/superresolution imaging of syndapin nanodomains, and domain/point-mutant rescue in neurons","pmids":["34264190"],"confidence":"High","gaps":["Functional division of labor between Cobl and Cobl-like not defined","How nanodomain geometry templates branch initiation not resolved"]},{"year":2021,"claim":"Established a causal role for COBL in adult dendritic repair, showing it is degraded by calpain after ischemia then re-expressed during a defined regrowth window required for recovery.","evidence":"Mouse MCAO model, Cobl KO, dendritic morphometry, calpain inhibition and mRNA quantification","pmids":["34898601"],"confidence":"High","gaps":["Signals driving the compensatory mRNA upregulation not identified","Whether restoring COBL therapeutically improves outcome not tested"]},{"year":2025,"claim":"Extended COBL's actin-organizing role to a non-neuronal epithelium, showing it shapes ameloblast cortical F-actin and enamel composition during amelogenesis.","evidence":"Cobl KO mouse, immunofluorescence colocalization, F-actin density quantification and enamel composition analysis","pmids":["40072087"],"confidence":"Medium","gaps":["No biochemical reconstitution in ameloblasts; partner dependence not tested","Single lab"]},{"year":2025,"claim":"Identified COBL as the first molecular requirement for a transient cortical dendritic arbor expansion during emerging adulthood, extending its developmental role into late brain maturation.","evidence":"Cobl KO mouse with time- and layer-resolved dendritic morphometry across cortical regions","pmids":["40555515"],"confidence":"Medium","gaps":["No direct biochemical mechanism in this study","Single lab; functional consequence of the missing expansion for behavior unknown"]},{"year":null,"claim":"How COBL's multiple regulatory inputs (Ca²⁺/CaM, PRMT2 methylation, syndapin I recruitment, calpain proteolysis, IGFN1 stabilization) are integrated into a single quantitative control of actin nucleation in vivo remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No integrated structural model of regulated COBL","Order and hierarchy of the regulatory layers not established","Mapping of specific methylation residues and CaM-binding sites onto nucleation output incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,3,4]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,7]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,9]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3,4]}],"complexes":[],"partners":["SDC1","DBNL","PRMT2","CALM1","COBLL1","IGFN1","WASL"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O75128","full_name":"Protein cordon-bleu","aliases":[],"length_aa":1261,"mass_kda":135.6,"function":"Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles","subcellular_location":"Cell membrane; Cytoplasm, cytoskeleton; Cell projection, ruffle; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/O75128/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/COBL","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"PACSIN3","stoichiometry":4.0},{"gene":"ACTG1","stoichiometry":0.2},{"gene":"PACSIN2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/COBL","total_profiled":1310},"omim":[{"mim_id":"610318","title":"COBL-LIKE PROTEIN 1: COBLL1","url":"https://www.omim.org/entry/610318"},{"mim_id":"610317","title":"CORDON-BLEU WH2 REPEAT PROTEIN; COBL","url":"https://www.omim.org/entry/610317"},{"mim_id":"601523","title":"GROWTH FACTOR RECEPTOR-BOUND PROTEIN 10; GRB10","url":"https://www.omim.org/entry/601523"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"},{"location":"Cell Junctions","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"skeletal muscle","ntpm":124.0},{"tissue":"tongue","ntpm":100.7}],"url":"https://www.proteinatlas.org/search/COBL"},"hgnc":{"alias_symbol":["KIAA0633"],"prev_symbol":[]},"alphafold":{"accession":"O75128","domains":[{"cath_id":"3.10.20.90","chopping":"56-139","consensus_level":"medium","plddt":88.8298,"start":56,"end":139},{"cath_id":"3.10.20.90","chopping":"153-230","consensus_level":"medium","plddt":88.2638,"start":153,"end":230}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O75128","model_url":"https://alphafold.ebi.ac.uk/files/AF-O75128-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O75128-F1-predicted_aligned_error_v6.png","plddt_mean":50.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=COBL","jax_strain_url":"https://www.jax.org/strain/search?query=COBL"},"sequence":{"accession":"O75128","fasta_url":"https://rest.uniprot.org/uniprotkb/O75128.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O75128/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O75128"}},"corpus_meta":[{"pmid":"21725280","id":"PMC_21725280","title":"The functions of the actin nucleator Cobl in cellular morphogenesis critically depend on syndapin I.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21725280","citation_count":62,"is_preprint":false},{"pmid":"23223303","id":"PMC_23223303","title":"The actin nucleator Cobl is crucial for Purkinje cell development and works in close conjunction with the F-actin binding protein Abp1.","date":"2012","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/23223303","citation_count":48,"is_preprint":false},{"pmid":"26334624","id":"PMC_26334624","title":"The Actin Nucleator Cobl Is Controlled by Calcium and Calmodulin.","date":"2015","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/26334624","citation_count":47,"is_preprint":false},{"pmid":"29689199","id":"PMC_29689199","title":"Arginine Methylation by PRMT2 Controls the Functions of the Actin Nucleator 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NI86/21.","date":"1994","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/8200543","citation_count":11,"is_preprint":false},{"pmid":"34898601","id":"PMC_34898601","title":"Poststroke dendritic arbor regrowth requires the actin nucleator Cobl.","date":"2021","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/34898601","citation_count":9,"is_preprint":false},{"pmid":"27419633","id":"PMC_27419633","title":"COBL is a novel hotspot for IKZF1 deletions in childhood acute lymphoblastic leukemia.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/27419633","citation_count":9,"is_preprint":false},{"pmid":"29198020","id":"PMC_29198020","title":"Identification of a novel intergenic miRNA located between the human DDC and COBL genes with a potential function in cell cycle arrest.","date":"2017","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29198020","citation_count":9,"is_preprint":false},{"pmid":"30877974","id":"PMC_30877974","title":"IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia.","date":"2019","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/30877974","citation_count":7,"is_preprint":false},{"pmid":"36834493","id":"PMC_36834493","title":"COBL, MKX and MYOC Are Potential Regulators of Brown Adipose Tissue Development Associated with Obesity-Related Metabolic Dysfunction in Children.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36834493","citation_count":5,"is_preprint":false},{"pmid":"38790240","id":"PMC_38790240","title":"Genome-Wide Identification and Hormone Response Analysis of the COBL Gene Family in Barley.","date":"2024","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/38790240","citation_count":3,"is_preprint":false},{"pmid":"40072087","id":"PMC_40072087","title":"The Evolutionary Young Actin Nucleator Cobl Is Important for Proper Amelogenesis.","date":"2025","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/40072087","citation_count":0,"is_preprint":false},{"pmid":"40555515","id":"PMC_40555515","title":"Emerging Adulthood Is Marked by a Cortical Dendritic Arborization Phase Depending on the Actin Nucleator Cobl.","date":"2025","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/40555515","citation_count":0,"is_preprint":false},{"pmid":"12652872","id":"PMC_12652872","title":"[Standardization of neutralization tests using the COBL cell line and comparison with the particle agglutination test for measles serology].","date":"2002","source":"Mikrobiyoloji bulteni","url":"https://pubmed.ncbi.nlm.nih.gov/12652872","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.09.25337647","title":"Machine-learning-based analysis of transcriptomics data for the identification of molecular signatures in cancer","date":"2025-10-10","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.09.25337647","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12897,"output_tokens":3390,"usd":0.04477,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10872,"output_tokens":3690,"usd":0.073305,"stage2_stop_reason":"end_turn"},"total_usd":0.118075,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"Cobl forms complexes with syndapin I in vivo (coimmunoprecipitation, colocalization, subcellular recruitment). Syndapin I recruits Cobl to membranes via its F-BAR domain (in vitro reconstitution and subcellular fractionation). Syndapin I RNAi impairs cortical localization of Cobl. Cobl, syndapin I, and N-WASP co-exist in one complex. Cobl-mediated functions in neuronal morphogenesis (dendritic arbor development) critically rely on syndapin I and on Arp3.\",\n      \"method\": \"Coimmunoprecipitation, colocalization, subcellular fractionation, in vitro reconstitution, RNAi knockdown with neuronal morphology readout\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (Co-IP, in vitro reconstitution, fractionation, functional RNAi rescue) in a single focused study\",\n      \"pmids\": [\"21725280\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Cobl plays a crucial role in Purkinje cell dendritic arborization (branch point number, density, and higher-order branching). Cobl physically associates with the F-actin-binding protein Abp1 (subcellular fractionation, protein interaction analysis, reconstitution, colocalization). Cobl-mediated dendritic branch induction critically relies on Abp1, and a Cobl mutant deficient for Abp1 binding fails to rescue Cobl loss-of-function phenotypes. Abp1-mediated F-actin association is required for Cobl function, as an Abp1 mutant supporting Cobl association but lacking F-actin binding also failed to rescue.\",\n      \"method\": \"Gene gun transfection in cerebellar slices, RNAi knockdown, subcellular fractionation, protein interaction/co-IP, subcellular reconstitution, colocalization, functional rescue with point mutants\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods including mutagenesis-based rescue experiments establishing functional requirement of the Cobl-Abp1 interaction\",\n      \"pmids\": [\"23223303\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"In zebrafish, Cobl and syndapin I colocalize at the base of forming cilia and are both required for formation of kinocilia and F-actin-rich stereocilia in lateral line sensory hair cells. Proper formation of ciliated sensory hair cell rosettes requires Cobl's syndapin I-binding Cobl homology domain and the actin-nucleating C-terminus of Cobl. Loss of Cobl or syndapin I causes similar lateral line defects, supporting they function together.\",\n      \"method\": \"Morpholino knockdown in zebrafish, scanning electron microscopy, colocalization, rescue experiments with domain mutants\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — parallel loss-of-function studies in zebrafish with domain-specific rescue experiments and EM phenotyping\",\n      \"pmids\": [\"23203810\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Cobl actin nucleation activity requires all three of its WH2 domains. Cobl is directly regulated by Ca2+/calmodulin (CaM): Ca2+/CaM modulates Cobl's actin-binding properties and promotes Cobl's interactions with syndapin I. CaM inhibitor studies showed Cobl-mediated dendritic branching is strictly dependent on CaM activity. Cobl-induced dendritic branch initiation was preceded by Ca2+ signals and coincided with local F-actin and CaM accumulations. CaM-binding-defective Cobl mutants failed to rescue Cobl loss-of-function phenotypes.\",\n      \"method\": \"Overexpression and rescue experiments in primary neurons and tissue slices, CaM inhibitor studies, Ca2+ imaging, in vitro actin binding/nucleation assays, mutagenesis of CaM-binding sites\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro biochemical reconstitution combined with mutagenesis-based neuronal rescue and live Ca2+ imaging in a single focused study\",\n      \"pmids\": [\"26334624\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Cobl is controlled by arginine methylation via PRMT2. PRMT2 associates with Cobl in an SH3 domain-dependent manner (coprecipitation, Co-IP, cellular and in vitro reconstitutions), and this promotes methylation of Cobl's actin-nucleating C-terminal domain. Cobl methylation is key for Cobl actin binding. PRMT2 phenocopies Cobl in gain- and loss-of-function dendritogenesis assays. Cobl-mediated dendritic arborization required complex formation with PRMT2 and PRMT2's catalytic activity.\",\n      \"method\": \"Coprecipitation, coimmunoprecipitation, cellular and in vitro reconstitution, gain- and loss-of-function in neurons, catalytic mutant of PRMT2, actin binding assays\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution of methylation, mutagenesis of catalytic domain, and multiple cellular assays establishing mechanistic requirement\",\n      \"pmids\": [\"29689199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Cobl is required for postnatal planar cell polarity refinement in cochlear hair cells. Cobl KO mice show reduced F-actin beneath the sensory apparatus, premature kinocilium retraction, and mispositioned basal bodies/centrioles during the critical period of hearing onset. Pericentriolar scaffold defects in Cobl KO mice are actin polymerization-dependent and Ca2+/calmodulin signaling-dependent.\",\n      \"method\": \"Cobl KO mouse analysis, F-actin staining, centriole/basal body positioning imaging, Ca2+/CaM inhibitor treatment, actin polymerization inhibitor treatment\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO mouse with mechanistic dissection using pharmacological inhibitors linking Cobl to actin polymerization and Ca2+/CaM pathways\",\n      \"pmids\": [\"30157434\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"COBL physically interacts with and is stabilized by IGFN1 in skeletal muscle. COBL localizes to the Z-disc in adult muscle. IGFN1 interaction prevents COBL's ability to form actin ruffles in COS7 cells. COBL is expressed in differentiating C2C12 myoblasts but not in proliferating cells. COBL loss-of-function C2C12 clones are able to fuse, indicating COBL is not essential for myoblast fusion.\",\n      \"method\": \"Pulldown with IGFN1 fragments followed by proteomics, co-IP validation, colocalization imaging, COS7 cell actin ruffle assay, COBL KO C2C12 clones\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — proteomic pulldown with validation by co-IP and functional assay in COS7 cells, single lab\",\n      \"pmids\": [\"32768501\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cobl and Cobl-like act interdependently in dendritic arbor development; neither alone is sufficient. Syndapin I physically links Cobl and Cobl-like by forming nanodomains at convex plasma membrane areas at protrusion bases and interacting with three motifs in Cobl-like, one of which is Ca2+/calmodulin-regulated. Cobl-like's N-terminal calmodulin-binding site and Ca2+/CaM-responsive syndapin-binding motif are both critical for Cobl-like's dendritogenic function.\",\n      \"method\": \"Co-IP, colocalization, TIRF/superresolution imaging of syndapin nanodomains, loss-of-function and rescue experiments with domain/point mutants in neurons\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, superresolution imaging, domain-specific mutagenesis-based rescue) establishing interdependence and physical linkage mechanism\",\n      \"pmids\": [\"34264190\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cobl is required for poststroke dendritic arbor repair in peri-infarct penumbral neurons. Ischemic stroke and excitotoxicity cause calpain-mediated proteolysis of Cobl, significantly reducing Cobl levels. Cobl levels are subsequently restored by increased mRNA expression. In Cobl KO mice, the dendritic repair window (day 2-4 post-stroke) passed without dendritic regrowth, demonstrating Cobl is causally required for poststroke recovery.\",\n      \"method\": \"Mouse MCAO model, Cobl KO mice, dendritic morphometry, calpain inhibitor treatment, mRNA quantification\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO mouse with causal rescue window analysis and identified proteolytic mechanism (calpain), replicated across multiple time points\",\n      \"pmids\": [\"34898601\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cobl is expressed in ameloblasts during amelogenesis, particularly during the secretory phase, and colocalizes with actin filaments at the cell cortex. Cobl KO causes increased ameloblast height, increased apical F-actin at P0, and reduced apical F-actin density during maturation phase. Cobl-deficient mice show altered enamel composition (increased carbon content) and increased enamel surface area, demonstrating Cobl's role in actin cytoskeletal organization during enamel formation.\",\n      \"method\": \"Cobl KO mouse analysis, immunofluorescence colocalization, F-actin density quantification, enamel composition analysis\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with cellular and compositional phenotypes but single lab, no biochemical reconstitution\",\n      \"pmids\": [\"40072087\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cobl KO mice lack a transient cortical dendritic arbor expansion that occurs during emerging adulthood (in layer V during adolescence and layer II/III during emerging adulthood in somatosensory, prefrontal, and motor cortex). This expansion is accompanied by transient dendritic spine length changes, linking the process to actin dynamics. Cobl is thus the first molecular component identified as required for emerging adulthood-related neuronal arbor changes during brain maturation.\",\n      \"method\": \"Cobl KO mouse, dendritic morphometry at multiple developmental time points across cortical layers\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with time- and layer-resolved phenotyping, but single lab and no direct biochemical mechanism in this study\",\n      \"pmids\": [\"40555515\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"COBL (Cordon-Bleu) is a WH2 domain-based actin nucleator that requires all three of its WH2 domains for activity; it is recruited to membranes by syndapin I (via its F-BAR domain), regulated by direct Ca²⁺/calmodulin binding (which modulates actin binding and promotes syndapin I interaction), and further controlled by PRMT2-mediated arginine methylation of its C-terminal nucleating domain; in neurons, Cobl works in concert with Abp1 (F-actin anchoring) and interdependently with Cobl-like (physically coordinated by syndapin I) to drive dendritic branch initiation and arborization, and is also required for sensory hair cell ciliogenesis, cochlear planar cell polarity refinement, poststroke dendritic repair, ameloblast cytoskeletal organization, and cortical dendritic arbor expansion during emerging adulthood.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"COBL (Cordon-Bleu) is a WH2 domain-based actin nucleator that drives membrane-coupled actin cytoskeletal remodeling underlying neuronal dendritic branching and ciliary/cortical morphogenesis [#0, #3]. Its nucleating activity requires all three of its C-terminal WH2 domains and is gated by multiple inputs: direct Ca\\u00b2\\u207a/calmodulin binding modulates its actin-binding properties and promotes its association with syndapin I, while PRMT2-mediated arginine methylation of the actin-nucleating C-terminal domain is required for efficient actin binding [#3, #4]. COBL is recruited to membranes by the F-BAR protein syndapin I and acts together with the F-actin-anchoring protein Abp1, with mutants defective for either partner failing to rescue loss-of-function phenotypes, establishing both interactions as functionally essential [#0, #1]. In dendritic arbor development COBL operates interdependently with its paralog Cobl-like, the two being physically linked by syndapin I nanodomains at convex protrusion-base membranes [#7]. Beyond dendritogenesis, COBL is required for sensory hair cell ciliogenesis and cochlear planar cell polarity refinement [#2, #5], poststroke dendritic repair where it is cleaved by calpain and re-expressed during a defined repair window [#8], ameloblast cortical actin organization during enamel formation [#9], and a transient cortical dendritic arbor expansion during emerging adulthood [#10]. In skeletal muscle COBL localizes to the Z-disc and is stabilized by IGFN1, which suppresses its actin-ruffling activity [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established how COBL, a cytosolic actin nucleator, is targeted to the membrane sites where it acts, answering how nucleation is spatially controlled during dendritic morphogenesis.\",\n      \"evidence\": \"Co-IP, colocalization, subcellular fractionation, in vitro reconstitution and RNAi with neuronal morphology readout\",\n      \"pmids\": [\"21725280\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve how syndapin I binding is itself regulated\", \"Structural basis of the Cobl\\u2013syndapin I\\u2013N-WASP complex not defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identified Abp1 as an essential F-actin-anchoring partner, showing COBL-nucleated actin must be physically coupled to existing filaments to induce dendritic branches.\",\n      \"evidence\": \"Gene gun transfection in cerebellar slices, RNAi, fractionation, reconstitution and point-mutant rescue\",\n      \"pmids\": [\"23223303\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and order of Cobl\\u2013Abp1\\u2013F-actin assembly unresolved\", \"Whether Abp1 coupling is required in non-Purkinje cell contexts not tested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Extended COBL function beyond dendrites to ciliogenesis, showing the same syndapin I-binding and actin-nucleating domains build F-actin-rich stereocilia and kinocilia in sensory hair cells.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish, scanning EM, colocalization and domain-mutant rescue\",\n      \"pmids\": [\"23203810\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking cortical actin nucleation to ciliary base assembly not defined\", \"Whether mammalian hair cells use the identical domain requirements not tested here\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined the catalytic requirement (all three WH2 domains) and a direct Ca\\u00b2\\u207a/calmodulin regulatory input, explaining how local Ca\\u00b2\\u207a signals trigger COBL-driven branch initiation.\",\n      \"evidence\": \"In vitro actin nucleation/binding assays, CaM inhibitor and Ca\\u00b2\\u207a imaging, CaM-binding mutant rescue in neurons\",\n      \"pmids\": [\"26334624\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream source of the triggering Ca\\u00b2\\u207a signal not identified\", \"Quantitative relationship between CaM occupancy and nucleation rate not measured\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Revealed a post-translational control layer in which PRMT2-catalyzed arginine methylation of the nucleating domain is required for COBL actin binding and dendritogenesis.\",\n      \"evidence\": \"Co-IP, in vitro and cellular methylation reconstitution, PRMT2 catalytic mutant and gain/loss-of-function in neurons\",\n      \"pmids\": [\"29689199\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific methylated arginine residues and their individual contributions not mapped\", \"Interplay between methylation and Ca\\u00b2\\u207a/CaM regulation not resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated an in vivo requirement for COBL in cochlear planar cell polarity refinement, tying its actin and Ca\\u00b2\\u207a/CaM functions to centriole/basal body positioning during the critical period of hearing onset.\",\n      \"evidence\": \"Cobl KO mouse, F-actin and centriole imaging, actin-polymerization and Ca\\u00b2\\u207a/CaM inhibitor treatment\",\n      \"pmids\": [\"30157434\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular link between cortical actin and basal body anchoring not defined\", \"Whether the same partner set (syndapin I, Abp1) operates here not tested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified IGFN1 as a muscle-specific stabilizing partner that localizes COBL to the Z-disc and suppresses its actin-ruffling activity, indicating context-dependent restraint of COBL function.\",\n      \"evidence\": \"IGFN1 fragment pulldown with proteomics, co-IP, colocalization, COS7 ruffle assay and COBL KO C2C12 clones\",\n      \"pmids\": [\"32768501\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; physiological consequence of COBL\\u2013IGFN1 at the Z-disc not established in vivo\", \"Mechanism by which IGFN1 blocks ruffling not defined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Resolved how COBL and its paralog Cobl-like coordinate during dendritogenesis, showing syndapin I nanodomains physically link the two factors at convex membrane bases and that neither is sufficient alone.\",\n      \"evidence\": \"Co-IP, TIRF/superresolution imaging of syndapin nanodomains, and domain/point-mutant rescue in neurons\",\n      \"pmids\": [\"34264190\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional division of labor between Cobl and Cobl-like not defined\", \"How nanodomain geometry templates branch initiation not resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Established a causal role for COBL in adult dendritic repair, showing it is degraded by calpain after ischemia then re-expressed during a defined regrowth window required for recovery.\",\n      \"evidence\": \"Mouse MCAO model, Cobl KO, dendritic morphometry, calpain inhibition and mRNA quantification\",\n      \"pmids\": [\"34898601\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Signals driving the compensatory mRNA upregulation not identified\", \"Whether restoring COBL therapeutically improves outcome not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended COBL's actin-organizing role to a non-neuronal epithelium, showing it shapes ameloblast cortical F-actin and enamel composition during amelogenesis.\",\n      \"evidence\": \"Cobl KO mouse, immunofluorescence colocalization, F-actin density quantification and enamel composition analysis\",\n      \"pmids\": [\"40072087\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No biochemical reconstitution in ameloblasts; partner dependence not tested\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified COBL as the first molecular requirement for a transient cortical dendritic arbor expansion during emerging adulthood, extending its developmental role into late brain maturation.\",\n      \"evidence\": \"Cobl KO mouse with time- and layer-resolved dendritic morphometry across cortical regions\",\n      \"pmids\": [\"40555515\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct biochemical mechanism in this study\", \"Single lab; functional consequence of the missing expansion for behavior unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How COBL's multiple regulatory inputs (Ca\\u00b2\\u207a/CaM, PRMT2 methylation, syndapin I recruitment, calpain proteolysis, IGFN1 stabilization) are integrated into a single quantitative control of actin nucleation in vivo remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No integrated structural model of regulated COBL\", \"Order and hierarchy of the regulatory layers not established\", \"Mapping of specific methylation residues and CaM-binding sites onto nucleation output incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 9]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"SDC1\",\n      \"DBNL\",\n      \"PRMT2\",\n      \"CALM1\",\n      \"COBLL1\",\n      \"IGFN1\",\n      \"WASL\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}